Phenotypes Associated with This Genotype

Genotype
MGI:3581125

• Allelic Composition: Galc^twi/Galc^twi
• Genetic Background: B6.CE-Galc^twi/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:108359 , J:126892 , J:170081 )

• Background Sensitivity: lifespan of mutants is 45.5 days; death is result of peripheral and cranial nerve palsy (J:108359)

• Background Sensitivity: the average lifespan of homozygotes in this study is 37 days (J:126892)

• median survival is 51 days (J:170081)

homeostasis/metabolism

decreased circulating insulin-like growth factor I level ( J:165361 )

• IGF-1 plasma levels are reduced by 37.6%

abnormal lipid level ( J:165361 )

• galactosylsphingosine accumulation, with 14 fold higher levels than in wild-type, in the long bones

abnormal sphingomyelin level ( J:165361 )

• increase in total sphingomyelin in femurs, and in most of the sphingomyelin and ceramide containing saturated-unsaturated fatty acids

abnormal enzyme/coenzyme activity ( J:108359 )

• levels of Ptgds2 activity are 3-fold higher in the cerebrum and 5-fold higher in the cerebellum of mutants compared to wild-type

behavior/neurological

impaired righting response ( J:108359 )

• mutants have poorer righting response compared to wild-type or Ptgds2/Galc double mutants

tremors ( J:108359 , J:126892 )

• mutants barely stagger with strong intentional tremor (J:108359)

• Background Sensitivity: mean age of onset 21 days (J:126892)

ataxia ( J:108359 )

abnormal gait ( J:126892 )

• Background Sensitivity: wobbly gait appears at approximately 28-30 days of age

paresis ( J:170081 )

• moribund mice develop spastic paresis

paraparesis ( J:126892 )

nervous system

abnormal microglial cell morphology ( J:108359 )

• microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination

abnormal brain morphology ( J:126892 )

• Background Sensitivity: lectin-positive macrophages are found in the cerebellum, pons, and medulla more severely on this genetic background than when outcrossed to CAST/EiJ

increased oligodendrocyte progenitor number ( J:170081 )

• mutants exhibit an increase in oligodendrocyte progenitor cell (OPC) population compared to wild-type

abnormal forebrain morphology ( J:170081 )

• levels of psychosine are increased in the forebrain while levels of free sphingosine are lower compared to wild-type mice

abnormal hindbrain morphology ( J:126892 )

• dramatically increased concentration of psychosine in the pons/medulla which is not impacted by genetic background

abnormal astrocyte morphology ( J:108359 , J:126892 )

• there are hypertrophied astrocytes with large soma and thick-branched processes in mutant brains (J:108359)

• Background Sensitivity: increased GFAP staining astrocytes are found in the cerebellar granular layer and pons (J:126892)

astrocytosis ( J:170081 )

• white matter exhibits similar reactive astrocytosis as double Galc^twi Csf1^op mice

abnormal oligodendrocyte morphology ( J:170081 )

• oligodendrocyte progenitor cells become hypertrophic and have short and stout processes instead of well branched fine processes as in wild-type mice

decreased oligodendrocyte number ( J:170081 )

• mutants exhibit a moderate decrease in oligodendrocytes

abnormal sciatic nerve morphology ( J:126892 )

• sciatic nerves are swollen and demyelination and myelin debris is found in moribund homozygotes

demyelination ( J:108359 , J:126892 , J:170081 )

• 39 day-old mutant brains exhibit demyelination; demyelination appears to be restricted to the CNS (J:108359)

• Background Sensitivity: extensive demyelination is found in the cerebellar white matter at the moribund stage on this genetic background (J:126892)

• myelin degeneration in the white matter, with a preferential loss of myelin in large diameter axons (J:170081)

• sciatic nerves are severely demyelinated (J:170081)

• however, development (wrapping) of myelin from P15 to P30 is not affected (J:170081)

hematopoietic system

abnormal microglial cell morphology ( J:108359 )

• microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination

abnormal osteoclast physiology ( J:165361 )

• enhanced osteoclast activity

immune system

abnormal microglial cell morphology ( J:108359 )

• microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination

abnormal osteoclast physiology ( J:165361 )

• enhanced osteoclast activity

growth/size/body

decreased body weight ( J:165361 )

• body weight is reduced starting at P20

weight loss ( J:170081 )

• mutants start to lose weight after P35

limbs/digits/tail

decreased femur size ( J:165361 )

• femurs are smaller

decreased femur weight ( J:165361 )

• femurs weigh 27% less than wild-type at 32-33 days of age

skeleton

decreased femur size ( J:165361 )

• femurs are smaller

decreased femur weight ( J:165361 )

• femurs weigh 27% less than wild-type at 32-33 days of age

abnormal long bone metaphysis morphology ( J:165361 )

• metaphyseal region of femurs show structural differences, with reduced trabecular bone mainly in the secondary spongiosa

decreased bone mineral density ( J:165361 )

• mice exhibit features of osteopenia

decreased compact bone thickness ( J:165361 )

• decrease in cortical bone thickness in femurs

decreased bone trabecula number ( J:165361 )

• decrease in the number of trabeculae in femurs

abnormal skeleton development ( J:165361 )

• growth of long bones is retarded

abnormal bone remodeling ( J:165361 )

• reduction of bone deposition in the metaphyseal and epiphyseal region of femurs, but no differences in mineral apposition rate

abnormal osteoclast physiology ( J:165361 )

• enhanced osteoclast activity

muscle

muscle twitch ( J:170081 )

• mutants develop fine twitching in the neck around P20

cellular

increased oligodendrocyte progenitor number ( J:170081 )

• mutants exhibit an increase in oligodendrocyte progenitor cell (OPC) population compared to wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Krabbe disease		DOID:10587	OMIM:245200	J:6390 , J:6423 , J:165361 , J:170081